Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of SU11248 in Patients Following Failure of Imatinib for Metastatic GIST

Trial Design: A phase 3, multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of SU11248 in patients with GIST following failure of Imatinib (due to objective disease progression or intolerable adverse effects of prior imatinib). SU11248 was administered at 50 mg/day for 4 weeks, followed by a 2-week break in each 6-week cycle, and was compared with placebo (randomization ratio of 2:1, SU112348 to placebo). Patients who progressed had their treatment unblinded and were offered crossover to receive SU11248 therapy.
Objective: To determine the efficacy of SU11248 in patients with imatinib-resistant GIST, or those intolerant to imatinib therapy
Number of Patients:
  • Intent-to-treat population: 312 (efficacy analysis)
    • SU11248: 207
    • Placebo:   105
  • As-treated population: 304 (safety analysis)
    • SU11248: 202
    • Placebo:   102
Key Inclusion Criteria:
  • Histologically-proven diagnosis of malignant GIST
  • Measurable disease
  • Demonstrated failure of prior treatment with imatinib (disease progression or significant toxicity)
  • Resolution of prior imatinib toxicity
  • ECOG performance score of 0 or 1
  • Adequate organ function
  • Age ≥ 18 years
Key Exclusion Criteria:
  • Other concurrent treatments for GIST
  • Diagnosis of other malignancy within the last 5 years
  • Significant cardiovascular disease
  • Positive for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
Results: All efficacy endpoints were achieved at the first interim analysis and treatment was unblinded following discussion between the Independent Data and Safety Monitoring Board and Study Sponsor (Pfizer)Blinded Phase

  • During the blinded phase, SU11248 was associated with a >4-fold increase in median time-to-progression (the primary endpoint of the trial) compared with placebo (6.3 vs 1.5 months; P<0.00001; hazard ratio [HR]=0.335
  • SU11248 significantly improved survival compared with placebo (P-0.00674; HR=0.491)
  • Non-hematologic adverse events that were more common in the SU11248 treated arm included low-grade fatigue, diarrhea, nausea, sore mouth, skin discoloration, and hand-foot effects and higher grade hypertension.
  • Hematologic adverse events that were more common in the SU11248 arm were neutropenia and thrombocytopenia, primarily low grade.


  • 59 placebo-treated patients opted to receive SU11248; patients in the SU11248 arm could continue if clinical benefit was perceived
  • 10% of placebo cross-over patients subsequently experienced a partial response

Overall response (Central Review Assessment)

Partial response 8 0
Stable disease 58 50
Progressive disease 20 39
Not evaluable
(too early or missing)
14 11
Principal Investigator: George D. Demetri, MD
Dana-Farber Cancer Institute
SU11248 Product Information: SU11248 is now approved in many countries and is available as Sutent®.

Core Values